Effect of lowering serum cholesterol on the composition of surfactant in adult rat lung.

Treatment of rats with 10 mg.kg body wt-1 day-1 4-aminopyrazolo[3,4-d]pyrimidine (APP) for 2 days markedly reduced serum cholesterol and phospholipids. This was associated with large decreases in the principal component of alveolar surfactant, the disaturated phospholipids (DSP), in the lamellar body and in the tubular myelin-rich and -poor alveolar fractions, but with no concomitant change in cholesterol or surfactant protein A. These decreases in DSP were associated with a decrease in the synthesis of surfactant phospholipids. Despite these large changes in composition of alveolar surfactant, we could detect no change in either static or dynamic lung compliance. However, the treatment markedly increased both the minimum and maximum surface tension of the lipid extract of the tubular myelin-rich fraction, as measured by bubble surfactometry. Whereas these changes appeared unimportant in the isolated perfused lung at resting tidal volume, they were associated with edema after an increase in tidal volume. The ability of APP to inhibit phospholipid synthesis selectively makes it a useful tool in investigating the surfactant system.